Kamlet-Taft (KT) parameters were measured for four nonaqueous hydrogen bond donor (HBD)-hydrogen bond acceptor (HBA) solvent-pair mixtures: methanol-cyclopentanone, methanol-cyclohexanone, ethanol-cyclopentanone, and ethanol-cyclohexanone to define their solvent polarity as a function of composition. KT mixed-solvent polarities differed greatly from molar average property values. The preferential solvation (PS) model was used to correlate solvent polarity and showed that local compositions of 1:1 (HBD-HBA) complex molecules were highly asymmetric. Trends of KT parameters of both cyclohexanone and cyclopentanone mixtures were similar, although the specific hydrogen bonding interactions of HBD-HBA complex molecules in cyclohexanone mixtures were stronger than those of cyclopentanone mixtures according to density functional theory calculations, infrared spectroscopy, and solution macroscopic properties. Application of the PS model to pharmaceuticals showed that the solvent-pair mixtures have wide-working composition ranges (∼0 < xHBA < ∼ 1) for aspirin, ibuprofen, niflumic acid, p-amino-benzoic, p-hydroxy-benzoic and salicyclic acid, limited composition ranges (ΔxHBA ≈ 0.7) for benzoic acid and temazepam, and narrow composition ranges (ΔxHBA ≈ 0.3) for others. By comparing mixed-solvent polarity with polarity of solvents being used for material, petroleum, and biomass processing, it can be concluded that cyclic ketone-alcohol mixtures have many applications.